Female mosquitoes must blood feed for oogenesis. The blood meal provides iron, but also allows infection and transmission of pathogens by these disease vectors. Mechanisms that allow females to adapt to the iron load in the presence of infectious agents are not known. We have found that mosquitos express iron regulatory protein 1 (IRP1) and the ferritin heavy (HCH) and light chain subunits. Like mammals, mosquito IRP 1 interacts with an iron regulatory element (IRE) found in the HCH mRNA and represses translation. In contrast to mammals, mosquitos secrete ferritin composed of the HCH subunits in response to an iron challenge. Our hypothesis is that mosquitoes avoid cellular iron overload by secreting ferritin and that the HCH is essential for this process and for cell survival. In mammals, ferritin expression is increased in response to infection and H chain expression up regulates expression of some immune factors. We have found that IRP1/IRE interaction is increased as part of the mosquito immune response. We think this reflects phosphorylation of IRP 1. We hypothesize that IRP 1 interaction with the HCH mRNA down regulates ferritin synthesis and compromises vector immunity. We propose the following specific aims to test our hypotheses: (1) To determine the importance of ferritin secretion and each subunit to mosquito survival following an iron challenge, (2) To characterize the effects of infection on IRP 1/IRE interaction and ferritin synthesis in vectors, and (3) To further characterize the mechanism(s) modulating IRP 1/IRE interaction and to obtain other messages that are controlled by IRP1/IRE interaction in mosquitoes. In the longer term, we want to determine how female mosquitoes adapt to an iron load in the presence of infectious agents and whether differences exist in this process between refractory and non-refractory mosquitoes. We also are interested in designing control strategies that modulate IRP1/IRE interaction or that interfere with ferritin synthesis or secretion. [unreadable] [unreadable]